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To obtain 3D CT measurements of mitral annulus throughout cardiac cycle using prototype mitral modeling software, assess interobserver agreement, and compare among patients with mitral prolapse (MP) and control group.Pre-procedural imaging is critical for planning of transcatheter mitral valve (MV) replacement. However, there is limited data regarding reliable CT-based measurements to accurately characterize the dynamic geometry of the mitral annulus in patients with MV disease.Patients with MP and control subjects without any MV disease who underwent ECG-gated cardiac CT were retrospectively identified. Multiphasic CT data was loaded into a prototype mitral modeling software. Multiple anatomical parameters in 3D space were recorded throughout the cardiac cycle (0-95%): annular circumference, planar-surface-area (PSA), anterior-posterior (A-P) distance, and anterolateral-posteromedial (AL-PM) distance. Comparisons were made among the two groups, with p 0.05 considered statistically significant. Interobserver agreement was assessed on ten patients using intraclass correlation coefficient (ICC) among 4 experienced readers.A total of 100 subjects were included: 50 with MP and 50 control. Annular dimensions were significantly higher in the MP group than control group, with circumference (144 ± 11 vs. 117±8 mm), PSA (1533 ± 247 vs. 1005 ± 142 mmA significant variation in the mitral annular measures between different cardiac phases and two groups was observed with excellent interobserver agreement.

Introduction COVID‐19 caused by SARS‐CoV‐2 is an ongoing global health emergency. Pre‐existing cardiovascular diseases (CVD) including hypertension have a higher risk for severe illness, cardiac damage, and death. Therefore, strategies for cardiovascular protection in COVID‐19 are urgently needed, in addition to the development of vaccines against COVID‐19. Previously, it has been reported that several SARS‐CoV‐1 genes including encoded Envelope (E) protein, open reading frame (ORF) 3a, are capable of forming viral channels in mammalian cells and damaging the cells via activation of apoptotic or endoplasmic reticulum (ER) stress signaling. In addition, SARS‐CoV‐1 patients are found to possess antibodies against ORF3a, indicating that this protein was expressed at the surface of the host cells. Moreover, a recent clinical report confirmed that SARS‐CoV‐2 can directly infect cardiomyocytes. However, the specific molecular mechanisms underlying the linkage between SARS‐CoV‐2 infection and cardiac risk are unclear. Hypothesis SARS‐CoV‐2 genes including ORF3a can be expressed in cardiomyocytes after virus infection, and subsequently dysregulate cardiac functions. Methods HEK293T cells and H9c2 cardiac myoblasts were transfected with ORF3a and utilized for biochemical, cell biological, and electrophysiological assays. Numerical model of rabbit ventricular action potential was used to evaluate the role of ORF3a on cardiac electrophysiology and arrhythmia. Results Although ORF3a sequences from SARS‐CoV‐1 and ‐CoV‐2 have 72% similarity, ORF3a from SARS‐CoV‐2 maintains high homology with SARS‐CoV‐1 in the protein sequences of the transmembrane domains and the pore, which are critical for forming ion channels. We found that SARS‐CoV‐2‐ORF3a is expressed at plasma membrane and outer mitochondrial membrane as assessed by protein fractionation, mitochondrial digestion, and live‐cell imaging. Whole cell patch clamp revealed that ORF3a can form K+‐permeable channels at the plasma membrane with similar channel properties as the endogenous transient outward K+ current (Ito). Moreover, numerical simulations suggest that increased Ito amplitude (mimicking increase of ORF3a expression) may dysregulate Ca2+ transient and increase the risk for early afterdepolarization in response to increased heart rate. Lastly, we found that ORF3a promotes apoptotic signaling activation, but not ER stress signaling, assessed by caspase activity and the expression of major ER chaperones, respectively. Conclusion ORF3a from SARS‐CoV‐2 forms K+‐permeable channels at the plasma membrane and dysregulates cardiac Ca2+ handling and electrophysiology. ORF3a can also be expressed at the mitochondria and activate oxidative stress signaling, which exacerbates the risk of arrhythmia. Targeting SARS‐CoV‐2 viroporins including ORF3a may reduce the risk of sudden cardiac death and cardiac damage in COVID‐19 patients with pre‐existing CVDs.

Paroxysmal atrial fibrillation (Paro. AF) is challenging to identify at the right moment. This disease is often undiagnosed using currently existing methods. Nonlinear analysis is gaining importance due to its capability to provide more insight into complex heart dynamics. The aim of this study is to use several recently developed nonlinear techniques to discriminate persistent AF (Pers. AF) from normal sinus rhythm (NSR), and more importantly, Paro. AF from NSR, using short-term single-lead electrocardiogram (ECG) signals. Specifically, we adapted and modified the time-delayed embedding method to minimize incorrect embedding parameter selection and further support to reconstruct proper phase plots of NSR and AF heart dynamics, from MIT-BIH databases. We also examine information-based methods, such as multiscale entropy (MSE) and kurtosis (Kt) for the same purposes. Our results demonstrate that embedding parameter time delay (&tau, ), as well as MSE and Kt values can be successfully used to discriminate between Pers. AF and NSR. Moreover, we demonstrate that &tau, and Kt can successfully discriminate Paro. AF from NSR. Our results suggest that nonlinear time-delayed embedding method and information-based methods provide robust discriminating features to distinguish both Pers. AF and Paro. AF from NSR, thus offering effective treatment before suffering chaotic Pers. AF.

Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN.